Live bacteria, such as probiotic bacteria or live attenuated pathogens, represent attractive vehicles for the delivery of a range of biologically active agents such as vaccine antigens, biologically active molecules or even DNA. The advantages inherent in bacterial delivery vehicles include oral administration and the sustained release of the compound over a protracted period of time, eliminating the need for repeat doses.
Current commercially available vaccines and medications are largely parenterally administered, require multiple doses and depend on medical staff and a cold chain. Live bacterial vehicles offer an alternative to conventional prophylactic and therapeutic agents in that they can be delivered orally, may only require a single dose and are able to deliver large molecules, for example, multiple antigens. In addition, bacterial vehicles are well suited to large-scale manufacture and formulation and are stable when lyophilised. These attributes make this form of delivery attractive and could result in increased compliance, greater distribution and reduced cost for a variety of vaccines and medications.
Several bacterial delivery systems have been proposed based on various bacteria including Shigella spp. (U.S. Pat. No. 7,235,234), Salmonella spp. (US Patent Application No. 20090022691) and Lactobacillus spp. (US Patent Application No. 20090074734), but there are a number of problems inherent in these systems.
In general, bacteria are manipulated to produce strains with the required characteristics for use as delivery vehicles. Importantly, the safety profile of the bacteria should be ensured. Traditionally bacteria for use as delivery vehicles have been attenuated to be less pathogenic or non-pathogenic; however, it is difficult to ensure the safety of these bacteria as virulence genes can be reacquired and result in the bacteria reverting to a virulent form with the ability to cause disease. Further, manipulating bacterial strains to be amenable to transformation or to colonise an animal model may result in the production of secondary undesirable characteristics, or at the very least hinder experimentation and delay transition of bacterial delivery vehicles into the clinic. For example, manipulation of a strain such that experiments can be performed in an animal model such as a mouse, may result in the strain not colonising the target host, typically humans. Accordingly, manipulating bacteria in order produce a strain with desired characteristics should be avoided where possible.
The inventors of the present invention have previously proposed the use of Helicobacter pylori in a bacterial delivery system (US Patent Application No. 20070134264), which solved a number of the problems identified above; however, while US Patent Application No. 2007013464 provides a wealth of information regarding the use of H. pylori as a bacterial delivery vehicle, the development of specific bacterial strains with specific characteristics would be useful.